Synthesis and potent antitumor activity of new arylamino derivatives of nor-β-lapachone and nor-α-lapachone
- 作者：Eufrâ ; nio N. da Silva Jú ; nior ; Maria Cecí ; lia B.V. de Souza ; Antô ; nio V. Pinto ; Maria do Carmo F.R. Pinto ; Marilia O.F. Goulart ; Francisco W.A. Barros ; Claudia Pessoa ; Letí ; cia V.
- 关键词：Lapachones ; Dihydrofuranonaphthoquinones ; Cancer ; Cytotoxicity
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 November 2007
- 卷：15
- 期：22
- 页码：7035-7041
- 文件大小：174 K
摘要
Several arylamino derivatives of nor-β-lapachone were synthesized in moderate to high yields and found to show very potent cytotoxicity against six neoplastic cancer cells: SF-295 (central nervous system), HCT-8 (colon), MDAMB-435 (breast), HL-60 (leukaemia), PC-3 (prostate), and B-16 (murine melanoma), with IC50 below 1 μg/mL. Their cytotoxicities were compared to doxorubicin and with their synthetic precursors, β-lapachone and nor-β-lapachone. The activity against a normal murine fibroblast L-929 showed that some of the compounds were selective against cancer cells. The absence of hemolytic activity (EC50 > 200 μg/mL), performed with erythrocyte suspensions, suggests that the cytotoxicity of the compounds was not related to membrane damage of mouse erythrocytes. For comparison purposes, one isomeric compound based on nor-α-lapachone was also synthesized and showed lower activity than the related ortho-derivative. The modified arylamino quinones appear as interesting new lead compounds in anti-cancer drug development.